This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. ABSTRACT This study is designed to assess whether fluconazole prophylaxis will decrease death or candidiasis among infants most at risk for candidiasis, those 750g. This study will monitor for safety while on study drug until death or discharge from the NICU. In addition neurodevelopment will be assessed in the surviving infants at 18-22 months. The multi-center nature of this trial will help control for variability in rates of candidiasis between centers due to different care practices. Total study time will be 3 years--18 months for enrollment and 18 months corrected age for neurodevelopmental follow-up. I. HYPOTHESIS Floconazole prophylaxis will decrease death or candidiasis among infants most at risk for candidiasis, those 750g. II. SPECIFIC AIMS OBJECTIVES AIM 1: Determine if fluconazole prevents death or candidiasis in premature infants Hypothesis 1: Fluconazole prophylaxis will result in an absolute reduction of 15% in death or candidiasis in neonates born less than 750g. AIM 2: Determine effect of fluconazole prophylaxis on neurodevelopmental impairment Hypothesis 2: Fluconazole prophylaxis will result in improved neurodevelopmental outcomes in survivors at 18-22 months corrected age AIM 3: Determine the safety and pharmacokinetics of fluconazole Hypothesis 3: A fluconazole dose of 6 mg/kg twice weekly will be a safe and appropriate dosage. AIM 4: Evaluate antifungal resistance due to fluconazole prophylaxis Hypothesis 4: There will be no difference in MIC between isolates from infants receiving placebo and fluconazole. AIM 5: Collect scavenged blood sample for studies of associations between genetic variation in infants who develop Candida infections and those who dont. Hypothesis 5: Infant who develop Candida infections will exhibit genetic variation when compared to infant who do not develop Candida infections.